Tumor-Infiltrating FoxP3+Tregs and CD8+T Cells Affect the Prognosis of Hepatocellular Carcinoma Patients

被引:94
作者
Huang, Yong [1 ,2 ]
Wang, Feng-mei [1 ,2 ]
Wang, Tao [2 ]
Wang, Yi-jun [3 ]
Zhu, Zheng-yan [4 ]
Gao, Ying-tang [4 ]
Du, Zhi [3 ,4 ]
机构
[1] Tianjin Med Univ, Cent Clin Coll 3, Tianjin, Peoples R China
[2] Third Cent Hosp Tianjin, Dept Gastroenterol & Hepatol, Tianjin 300170, Peoples R China
[3] Third Cent Hosp Tianjin, Dept Hepatobiliary Surg, Tianjin 300170, Peoples R China
[4] Third Cent Hosp Tianjin, Key Lab Artificial Cell, Inst Hepatobiliary Dis, Tianjin 300170, Peoples R China
关键词
Carcinoma; Hepatocellular; FoxP3; CD8; Angiogenesis; Prognosis; REGULATORY T-CELLS; CHRONIC HEPATITIS; PERIPHERAL-BLOOD; INCREASED POPULATIONS; IMMUNE-RESPONSE; LIVER; EXPRESSION; CANCER; LYMPHOCYTES; TOLERANCE;
D O I
10.1159/000342801
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Purpose: Tumor-infiltrating lymphocytes are considered to represent a host immune response against tumor. This study was carried out to analyze the effect of both FoxP3+ regulatory T cells (Tregs) and CD8+ T lymphocytes in prognostic value of hepatocellular carcinoma (HCC) patients. Methods: Expressions of FoxP3, CD4, CD8 and CD34 in patient-matched tumors and peritumoral tissues were assessed by immunohistochemistry for 54 HCC patients. The prognostic effect of groups with high and low numbers was evaluated by the Kaplan-Meier and Cox model analysis using median values as a cutoff. Results: Compared with the corresponding pentumoral tissue, tissue, the density of intratumoral Tregs was significantly higher, while the density of intratumoral CD8+ T cells was lower (p <0.001 and p = 0.013, respectively). In addition, tumor-infiltrating Tregs were positively correlated with microvessel density in tumors (r = 0.334, p = 0.020). The high intratumoral Tregs density group showed a significantly lower survival rate (overall survival, p = 0.018; disease-free survival, p = 0.029). Multivariate Cox analysis revealed that intratumoral Tregs density was an independent prognostic factor for HCC. Conclusions: Tumor-infiltrating Tregs may promote HCC progression by fostering angiogenesis and decreasing CD8+ T cells. High tumor-infiltrating Tregs are thought to be an unfavorable prognostic indicator for HCC. Copyright (C) 2012 S. Karger AG, Basel
引用
收藏
页码:329 / 337
页数:9
相关论文
共 47 条
[1]   CD8+T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells [J].
Antony, PA ;
Piccirillo, CA ;
Akpinarli, A ;
Finkelstein, SE ;
Speiss, PJ ;
Surman, DR ;
Palmer, DC ;
Chan, CC ;
Klebanoff, CA ;
Overwijk, WW ;
Rosenberg, SA ;
Restifo, NP .
JOURNAL OF IMMUNOLOGY, 2005, 174 (05) :2591-2601
[2]   Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[3]   Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm [J].
Biswas, Subhra K. ;
Mantovani, Alberto .
NATURE IMMUNOLOGY, 2010, 11 (10) :889-896
[4]   Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment [J].
Budhu, Anuradha ;
Forgues, Marshonna ;
Ye, Qing-Hai ;
Jia, Hu-Liong ;
He, Ping ;
Zanetti, Krista A. ;
Kammula, Udai S. ;
Chen, Yidong ;
Qin, Lun-Xiu ;
Tang, Zhao-You ;
Wang, Xin Wei .
CANCER CELL, 2006, 10 (02) :99-111
[5]   Regulatory T cells and the liver: A new piece of the puzzle [J].
Chang, KM .
HEPATOLOGY, 2005, 41 (04) :700-702
[6]   Depletion of CD4+CD25+ regulatory T cells can promote local immunity to suppress tumor growth in benzo[a]pyrene-induced forestomach carcinoma [J].
Chen, Yi-Ling ;
Fang, Jung-Hua ;
Lai, Ming-Derg ;
Shan, Yan-Shen .
WORLD JOURNAL OF GASTROENTEROLOGY, 2008, 14 (38) :5797-5809
[7]   The Liver as a Lymphoid Organ [J].
Crispe, Ian Nicholas .
ANNUAL REVIEW OF IMMUNOLOGY, 2009, 27 :147-163
[8]   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Evdemon-Hogan, M ;
Conejo-Garcia, JR ;
Zhang, L ;
Burow, M ;
Zhu, Y ;
Wei, S ;
Kryczek, I ;
Daniel, B ;
Gordon, A ;
Myers, L ;
Lackner, A ;
Disis, ML ;
Knutson, KL ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[9]   Regulatory T Cell as a Target for Cancer Therapy [J].
Dias de Rezende, Lucas Cunha ;
Silva, Ian Victor ;
Azevedo Rangel, Leticia Batista ;
Cunegundes Guimaraes, Marco Cesar .
ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS, 2010, 58 (03) :179-190
[10]   Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells [J].
Facciabene, Andrea ;
Peng, Xiaohui ;
Hagemann, Ian S. ;
Balint, Klara ;
Barchetti, Andrea ;
Wang, Li-Ping ;
Gimotty, Phyllis A. ;
Gilks, C. Blake ;
Lal, Priti ;
Zhang, Lin ;
Coukos, George .
NATURE, 2011, 475 (7355) :226-U141